Chronic Intermittent Hypoxia increases oxidative stress and inflammation

Background: Inflammation has been linked with sleep apnea. Sleep apnea is a common comorbidity associated with neurodegenerative disorders, such as Parkinson’s disease and Alzheimer’s disease. Furthermore, neurodegenerative diseases have also been linked with inflammation. A possible mechanism underlying increased inflammation in these disorders is oxidative stress, a hallmark of neurodegeneration. To examine the role of oxidative stress on inflammation, we used chronic intermittent hypoxia (CIH), an established model for the hypoxemia associated with sleep apnea. CIH consists of recurring events of low oxygen followed by reoxygenation. Statement of Hypothesis: We hypothesize that CIH causes oxidative stress, which induces inflammation. Materials and methods: To test this hypothesis, plasma from adult male rats subjected to 7 days of CIH (3 minute periods of hypoxia (10% oxygen) and 3 minute periods of normoxia (21% oxygen) for 8 hours per day) or normoxia (room air) were tested for AOPP, an indicator of oxidative stress, and circulating inflammatory markers (such as IL-1b, IL-10, IL-4, IL-6). Additionally, a group of rats was administered a neurotropic AAV with shRNA for AT1a receptors in their forebrains and instrumented with telemetry for blood pressure recording prior to CIH treatment to determine the effects of angiotensin on CIH hypertension and oxidative stress. Significant results: Our results showed that CIH significantly increased circulating oxidative stress and inflammation. Interestingly, IL-1b, IL-2, and TNF-a inflammatory markers were associated with oxidative stress, unlike IL-10, IL-4, and IL-6 inflammatory markers. These markers were positively associated with IL-1b. Knockdown of angiotensin 1 receptors in the forebrain blocked the diurnal hypertension and CIH induced oxidative stress, indicating the involvement of CIH hypertension and central angiotensin receptors in CIH induced oxidative stress. Conclusions: These results indicate that both neurons and macrophages contribute to CIH induced oxidative stress and inflammation and that CIH oxidative stress and inflammation is dependent on central angiotensin receptors and CIH hypertension.